Proposed is a Mentored Scientist Career Development Award (K01) that provides me with the research experience and training necessary to develop an innovative research program focused on the co-occurring developmental trajectories of substance use disorders (SUDs) and associated common psychiatric disorders over the life course. My professional background has thus far focused on social epidemiology, and through the K-Award, I hope to integrate developmental psychopathology as a core component of my training. I will use the K01 to develop and test a model of the longitudinal relations between SUDs and common forms of psychopathology, and of the factors - from the community to the individual level - that drive patterns of comorbidity. My long-term career goal is to develop the training and experience needed to execute a research agenda that propels the field toward a deeper understanding of the mechanisms, from the community to the cellular level, that shape the development of SUDs and psychiatric disorders. Throughout my career and training thus far, I have researched how social factors at multiple levels, from the family to the neighborhood, shape life course trajectories of risk behaviors. As my work in the area has progressed, I have become aware that populations that engage in risk behaviors such as substance use rarely present a single problem: they suffer from a range of mental health problems, including conduct disorder, use, anxiety and depression. Therefore, I have become increasingly interested in assessing the determinants of comorbidity among SUDs and common mental illnesses, in particular during key developmental transitions from childhood to adulthood. In order to develop an independent program of research in this new area, I require additional training. I propose to engage in training in: 1) the natural history of SUDs and common psychiatric disorders; 2) a basic understanding of the genetic and neurobiologic sources of the disorders; 3) the ways the social environment shapes the genetic and neurobiologic mechanisms underlying SUDs and psychiatric disorders; and 4) techniques to collect primary data on aspects of the social environment that may influence SUDs and psychiatric disorders, and in the design and implementation of population-based cohort studies. Training will take place through: graduate-level courses in developmental psychopathology, epidemiology of substance use disorders, and genetic epidemiology; attending short courses on study design, advanced longitudinal data analysis and geostatistics; one-on-one tutorials with mentors in each area; and mentored implementation of the three studies outlined in the research plan of the K01. The research project aims to identify potentially modifiable risk factors for the development of comorbidity between SUD stages (initiation, use, abuse, and dependence) and symptoms of common psychiatric disorders from childhood to young adulthood. One-third to one-half of persons with any mental disorder have met criteria for another mental or substance use disorder at some point in their lives. Conducting research on comorbidity is critical if we are to improve diagnosis, provide adequate treatment and prevent substance use and comorbid psychiatric disorders. Yet the nature of the relationships between psychiatric disorders remains largely unknown. Thus, our ability to intervene to prevent or treat comorbid substance use and psychiatric disorders is limited. To achieve the general research aim, I propose a program of research that consists of three interrelated studies. Study 1 aims to determine the extent to which SUD stages from adolescence to young adulthood are associated with high symptom levels of common psychiatric disorders in childhood and adolescence. Study 2 aims to examine the relative influence of adverse individual and interpersonal characteristics, as well as neighborhood economic characteristics, on comorbidity between high symptom levels of common psychiatric disorders and SUD stages. Studies 1 and 2 will use data from the youngest (n=503) and oldest (n=506) cohorts of the Pittsburgh Youth Study (PYS), aged 7 and 13 respectively at baseline and followed biannually and then annually until the youngest cohort was 20 and the oldest was 25.5 years of age. I will apply latent class growth curve analysis to determine how initial symptom levels and rate of change in one psychiatric disorder are associated with the initial level and rate of change of drug use severity, and vice versa. Latent transition analysis will be used to test how psychiatric symptoms are associated with transitions across SUD stages. Study 3 aims to examine the relationship between the neighborhood physical and social environment and the risk of sequential comorbidity between common psychiatric disorders and substance dependence. I will develop, validate and field an instrument to conduct objective ratings of urban blocks in Baltimore City, to measure community factors that are theoretically linked to risk of substance use and psychiatric problems. Using data from the 2nd generation Johns Hopkins Preventive Intervention Research Center (JHU PIRC) cohort, a sample of high-risk urban adolescents (n=398), I will test whether neighborhood characteristics, as measured by my instrument, explain, mediate or modify the relationship between adolescent psychiatric disorders and substance use disorder status in young adulthood. Research on the distribution of comorbid psychiatric and SUD stages in different types of neighborhoods can provide a firm foundation for addressing broader questions such as differences by race/ethnicity, nationality or socio-economic status in levels of substance abuse and dependence.